PIK3CD L666P

c.1997T>C NM_005026.4 PI3K-AKT transition, gain of function

Cancer hotspot Not a hotspot missense variant. Genome Nexus / cancerhotspots.org

Population · gnomAD 6.8e-7 gnomAD v4

ClinVar Not in ClinVar no exact-match submission

Protein region PIK helical Residue 666 of PIK3CD. UniProt O00329

AlphaMissense likely pathogenic Pathogenicity score 0.99. Computational prediction, not clinical evidence.

Position in PIK3CD 1 catalogued

Reported in LM

ISSVA subset	Allele fraction	Sources
LM	2-3%	PMC8106842

Bars show the reported allele-fraction range on a 0 to 50 percent axis.

Pathway and targeted therapy

Driver of the PI3K-AKT pathway. Repurposed drugs already used in the clinic for this pathway: alpelisib (PI3Kα inhibitor), sirolimus (mTOR inhibitor).

Open and recent trials (3 in vascular / lymphatic anomalies for alpelisib)

Alpelisib in Pediatric and Adult Patients With Lymphatic Malformations Associated With a PIK3CA Mutation. RECRUITING NCT05948943 · PHASE2, PHASE3
A Trial of Targeted Therapies for Patients With Slow-Flow or Fast-Flow Vascular Malformations RECRUITING NCT05983159 · PHASE2
24VA022; VATCH Alpelisib for TIE2/PIK3CA Pathway VAs ACTIVE NOT RECRUITING NCT07543822 · PHASE2

Primary sources (1)

A somatic mutation in PIK3CD unravels a novel candidate gene for lymphatic malformation.
Wang S, Wang W, Zhang X, Gui J, Zhang J, Guo Y, Liu Y, Han L, Liu Q, Li Y, Sun N, Liu Z, Du J, Tai J, Ni X. · Orphanet J Rare Dis · 2021

Mentioned in 1 publications indexed by Europe PMC.

Cross-references

gnomAD · PIK3CD ClinVar · L666P OncoKB cBioPortal · PIK3CD VarSome UniProt · PIK3CD AlphaFold · PIK3CD